A Study to Test if a Third Dose of the Vaccine is Safe in Current and Former Smokers Aged 40 to 80 Years Old and to Gather Information on the Immune Response Following the Third Dose of the Vaccine

The purpose of this Phase 2 study is to evaluate two vaccine schedules of the investigational NTHi-Mcat vaccine. As the prevalence of COPD increases with age and as age has an influence on both the immunogenicity and reactogenicity of a vaccine, subjects 40-80 years old will be enrolled. As cigarette smoking is the most commonly encountered risk factor for COPD, adults with a smoking history of at least 10 pack-years will be selected in order to immunologically match the COPD population as much as possible. Literature data indeed suggest that alterations of the immune system start early on in smokers, before the COPD disease is recognized \[Barcelo et al 2008; Droemann et al, 2005; Takanashi et al, 1999\]. Several formulations of a vaccine containing the NTHi antigens (10 or 30 µg) either non-adjuvanted or combined with different adjuvants (aluminium \[Al\], adjuvant system \[AS\]01E and AS04C) were already evaluated in two previous Phase 1 clinical trials (NTHI-002 in healthy adults aged 18 - 40 years and NTHI-003 in current and former healthy smokers of 50-70 years old). The investigational vaccines were well-tolerated, with an acceptable safety and reactogenicity profile. These studies allowed the dose selection of the NTHi antigens (10 µg) and the adjuvant system (AS01E) evaluated for the first time in moderate and severe COPD patients aged 40-80 years in the Phase 2 study NTHI-004. The safety, reactogenicity and immunogenicity of different formulations of the NTHi-Mcat investigational vaccine have been evaluated in the Phase 1 study in healthy adults aged 18-40 years and in current and former smokers aged 50-70 years (study NTHI MCAT-001). Based on results obtained up to 30 days post-Dose 2 from this study, the AS01E-adjuvanted formulation containing 10 µg of NTHi proteins PD and PE-PilA and 3.3 µg of UspA2 has been selected for evaluation in the current NTHI MCAT-008 study. The current study will evaluate the impact of a 3rd dose (following a 0-2 month vaccination schedule), either given at 6 months or at 12 months after the first dose. The primary aim is to assess the safety of the additional dose. The study will also investigate how the two schedules improve the persistence of antibody response. To this end, adults aged 40 to 80 years with a smoking history of at least 10 pack-years, will receive 2 doses of the NTHi-Mcat investigational vaccine at 0 and 2 months in both study arms. Following these 2 doses, one study arm will receive a 3rd dose of the investigational NTHi-Mcat vaccine at 6 months and a placebo control at 12 months (Schedule 1) and the other study arm will receive a placebo control at 6 months and a 3rd dose of the investigational NTHi-Mcat vaccine at 12 months (Schedule 2).